PANCREATIC NEUROENDOCRINE CARCINOMA WITH SOLID-PSEUDOPAPILLARY FEATURES.
Pancreatic neuroendocrine tumors (PNT), also known as islet cell tumors, make up very small fraction of all pancreatic neoplasms1. Based on the function of pancreatic hormone secretion, PNTs are generally divided into functioning and non-functioning categories. The former includes insulinoma (beta cell), the most common type, and glucagonoma (alpha cell), gastrinoma (G cell), vipoma (VIP-producing cells). Most of beta cell tumors are benign while the majority of others including non-functioning ones are malignant 1, 2, 3. Depending on their growth patterns, PNTs are also divided into solid, gyriform and glandular patterns1, 2. Rarely, as presented in the current case, the tumor may show pseudopapillary features with fibrovascular core at the center and neoplastic cells at the peripheral. Tumor cells are usually composed of small relatively uniform cuboidal cells with centrally located nuclei and acidophilic finely granular cytoplasm. Evidence of invasion of tumor into peripancreatic tissue and adjacent organs is only reliable feature for the malignancy 1, 2, 3, 4.
Differential diagnosis of the PNT over other pancreatic tumor such as duct carcinoma, acinar cell carcinoma and intraductal papillary mucinous tumor etc. usually does not present significant problems because each type displays distinct features. The challenge is to distinguish it from solid-pseudopapillary tumor (SPTs) especially when the PNTs show areas of solid-pseudopapillary features (Figs. 5, 6, 7) as described in the current case. Distinguishing between these two types of tumors is clinically important because the SPTs usually have much better prognosis, even with a large tumor burden or with metastases 4, 5.
Solid-pseudopapillary tumor (SPT), also known as papillary and solid epithelial neoplasm, papillary cystic neoplasm/cystic solid papillary carcinoma, and Gruber-Frantz tumor, is often found in young women 1, 2, 3, 4. Grossly it is usually large and soft with cystic foci. Areas of hemorrhage and necrosis are often seen. The tumor is often encapsulated with an occasional infiltrative boarder. Microscopically the tumor cells shows distinctive feature of pseudopapilla with central vascular cores , covered with several layers of epithelial cells, most of which have ovoid and folded nuclei with inconspicuous nucleoli. Perivascular areas usually show significant myxoid degeneration and sometimes with cyst formation 1, 2, 3. Large numbers of eosinophilic globules are sometimes present. Occasional aggregates of histocytes and cholesterol clefts can be seen. Immunohistochemically these tumor cells have been reported to express both exocrine and endocrine hormones including chymotrypsin, trypsin, synaptophysin and neuron-specific enolase (NSE), which makes the differential diagnosis even harder from the neuroendocrine tumors.1, 2, 3
A recent study by Notohara, E. et al compared extended the immunohistochemical profile of 19 cases of SPTs and 20 cases of PNTs and found a very useful panel of immunohistochemical stains that can distingusih these entities in most of the difficult cases4. As simplified in the table below, SPTs are usually strongly and diffusely positive for CD10, CD56 and vimentin, and weakly and focally positive for synaptophysin and pan-CK, and negative for chromogranin. In contrast, PNTs are strongly and diffusively positive for synaptophysin, chromogranin, pan-CK, CD56 and negative for vimentin and CD10. The immunohistochemical profile for the current case best fits into PNTs even though the tumor cells showed typical solid pseudopapillary features.
In summary, we have presented a case of pancreatic neuroendocrine carcinoma with unusual solid pseudopapillary features, which raised an interesting and challenging differential diagnosis with solid pseudopapillary carcinoma. We have showed that a panel of immunohistochemical stains is essential to reach a correct diagnosis.
Contributed by Zhengbin Lu, MD, Anthony J. Demetris, MD